Carbohydrates vs. fats and proteins: which causes more insulin release?

A new study published in Cell Metabolism sheds light on how different macronutrients—carbohydrates, proteins, and fats—can influence insulin secretion.

The study examined insulin responses in pancreatic islets from deceased donors, both with and without type 2 diabetes, and in pancreatic islets derived from stem cells.

Pancreatic islets are small clusters of cells in the pancreas, including beta cells, which play a key role in regulating blood sugar levels by producing hormones such as insulin and glucagon in response to nutrients.

It has long been known that carbohydrates have a significant impact on blood sugar levels, causing a surge in insulin, while proteins have a moderate effect and fats have minimal immediate effect.

However, this study suggests that insulin secretion in response to nutrients may be more complex and individualized than previously thought.

For the first time, researchers have identified subsets of human pancreatic islets that exhibited a greater insulin response to proteins or fats than to carbohydrates.

While laboratory studies on pancreatic islets may not translate directly to living people, the results could have significant implications for future personalized nutrition strategies to better control blood sugar levels, ultimately improving overall health outcomes.

Effect of each macronutrient on insulin responses

Researchers from the University of British Columbia have studied how human pancreatic islets secrete insulin in response to different nutrients.

Between 2016 and 2022, the researchers studied pancreatic islets from 140 deceased donors of varying ages, including those with and without type 2 diabetes.

They exposed the islets to glucose (carbohydrates), amino acids (proteins) and fatty acids (fats), monitoring insulin secretion.

The researchers also analyzed changes in gene expression in pancreatic cells from donors with and without type 2 diabetes to understand their impact on insulin production.

Using ribonucleic acid (RNA) sequencing and proteomics analysis, they measured more than 20,000 mRNAs and about 8,000 proteins. This helped them assess the relationship between insulin production and changes in gene expression in pancreatic islet samples.

Macronutrients induce unique insulin responses in pancreatic cells

According to current understanding, most donor islets showed the strongest insulin response to glucose, a moderate response to amino acids, and a small response to fatty acids.

As expected, compared with islets from non-diabetic donors, islets from type 2 diabetic donors had fewer insulin-producing beta cells, a delayed insulin peak in response to high glucose, and an overall lower glucose response.

While most of the results were predictable, there were some surprising results.

About 9% of donor pancreatic islets responded more strongly to proteins than to carbohydrates, and 8% responded more strongly to fats.

The islets that responded more strongly to the proteins were often from donors with type 2 diabetes but had similar long-term blood sugar levels (measured by HbA1c) as the others. However, this increased response to the proteins was associated with longer culture times in the lab.

On the other hand, islets that responded more strongly to fats were usually from donors with worse HbA1c values, but were otherwise similar to other donors. The researchers speculate that this response to fats may be related to beta cell immaturity, as seen in immature stem cell-derived islets.

To investigate the source of variation, they compared donor characteristics and found no differences in body mass index (BMI) or age. However, they did observe sex differences in insulin responses.

Specifically, compared with men, islets from female donors secreted less insulin in response to moderate glucose exposure, meaning their cells were less efficient at producing insulin.

This may be related to known sex differences in diabetes, but the reasons for this remain to be determined.

How can the results be applied to living people?

Discussing the potential relevance to living people, Dr. Jason Fung, a physician and best-selling author of The Obesity Code and The Diabetes Code, who was not involved in the study, noted: “Deceased donors are considered to be representative of the general population. That’s a reasonable assumption, but not necessarily true.”

Dr. Thomas M. Holland, a physician-scientist and associate professor at the RUSH Institute for Healthy Aging at RUSH University, who was also not involved in the study, provided further details.

"The results from the study on islets from deceased donors offer really valuable insights into insulin production in response to different macronutrients [but] there are limitations in directly translating these results to living people," he told MNT.

The internal environment of living organisms, including factors such as blood flow, levels of hormones for signaling, and nervous system interactions, can influence insulin responses and may differ from the “isolated” environment of beta islets. Although the study highlights variability among individuals, living humans experience additional influences such as lifestyle, diet, stress, and physical activity that may further modulate our insulin responses.

"In addition, deceased donors may not perfectly represent the healthy population, especially if they had underlying diseases that could affect pancreatic function," he noted.

The study authors also acknowledged limitations in applying their results, such as the lack of confirmed diagnoses of type 2 diabetes in organ donors and the absence of any human clinical trials to confirm their findings.

What implications does this have for practicing physicians and the public?

"The results of this study open the possibility for a more individualized dietary care plan to treat diabetes," said Sheri Gou, RDN, CDCES, a registered dietitian, certified diabetes care and education specialist, and owner of The Plant Strong Dietitian, who was not involved in the study.

Fung also emphasized that the findings of this study could have significant implications for dietary choices.

"Insulin can cause weight gain, and for most people, reducing refined carbohydrate intake is a very good way to lower insulin levels and induce weight loss. But for some people, a low-fat diet may be more effective," he explained.

The study authors, on the other hand, suggested that protein-rich diets could be beneficial for people with type 2 diabetes based on their findings. However, they stressed the need for further research.

Ultimately, "traditional diabetes diets focus on carbohydrate control based on the well-established link between glucose and insulin secretion, particularly from refined grains and sugar," but this study suggests the need for individualized approaches based on individual insulin responses to different macronutrients, Holland said.

"The difference is largely genetically determined, as the study indicates," Fung agreed.

On this point, Gou said: "In the future, there may be genetic tests that a doctor can use to determine the best macronutrient ratio for an individual's insulin response."

In the meantime, Holland advises people to follow current dietary recommendations with an open mind to making adjustments. Work closely with your primary care physician or registered dietitian to determine the dietary patterns and lifestyle changes that best support your unique needs for healthy blood sugar levels and optimal health.